1. Field of the Invention
This invention relates to methods of sterilization of medical devices, and particularly stents, a type of implantable medical device, and methods of preparing sterilized, packaged medical devices, including sterilized, packaged stents.
2. Background
This invention relates to methods of sterilization of articles, particularly medical devices, and more particularly, stents. In addition this invention relates to methods of preparing sterilized, packaged articles, and more particularly sterilized, packaged medical devices, including sterilized, packaged stents.
The term sterilization refers to the elimination of microorganisms such as fungi, bacteria, viruses and prions, or a reduction in the bioburden of an item where bioburden refers to the number of micro-organisms with which the item is contaminated. The degree of sterilization is typically measured by a sterility assurance level (SAL) which refers to the probability of a viable microorganism being present on a product unit after sterilization.
There are a number of sterilization procedures. The broad categories include heat, chemicals, irradiation, and filtration. An example of using heat to sterilize is autoclaving of medical instruments. Cooking or canning food is also another application of using heat for sterilization. A number of chemicals can be used for sterilization including ozone, chlorine bleach (sodium hypochlorite), formaldehyde/glutaraldehyde, ethylene oxide, hydrogen peroxide, and peracetic acid. Irradiation includes exposure to gamma rays, X rays, or ultraviolet rays or electron beam (Victoria Reitz, “Sterilization for Beginners,” June 18, Medical Design Magazine). Filtration typically involves filtering through a 0.2 micron filter.
The choice of sterilization technique will depend upon the application, and the sterility level desired. The required SAL for a product is dependent on the intended use of the product. For medical devices in particular, the level of sterility for a Class I device as per United States Food and Drug Administration (“FDA”) classifications, which presents a minimal risk of harm to the user and are simpler than Class II and Class III devices, will be different than the level required for a Class III device which “are usually those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury.” (FDA definition).
In addition the United States FDA regulates devices with most regulations for medical devices and radiation emitting products found Title 21 of the Code of Federal Regulations (CFR) parts 800-1299. Although the FDA does provide some guidance on sterility levels, more specific information can be found in guidance documents provided by the International Organization of Standards (ISO) documents which were developed in conjunction with Association for the Advancement of Medical Instrumentation (AAMI) (Reitz). SALs for various medical devices can be found in materials from the AAMI in Arlington, Va.
One type of medical device for which sterilization is required is a stent. A stent is a medical device belonging to the larger category of devices referred to as “endoprotheses.” An “endoprosthesis” corresponds to an artificial device that is placed inside the body. Stents are shaped devices which function to hold open, and sometimes expand, a segment of a blood vessel or other anatomical lumen such as urinary tracts and bile ducts. A “lumen” refers to a cavity of a tubular organ such as a blood vessel. A stent is a Class III medical device per FDA medical device classifications. Stents are often used in the treatment of atherosclerotic stenosis in blood vessels. “Stenosis” refers to a narrowing or constriction of the diameter of a bodily passage or orifice. In such treatments, stents reinforce body vessels and prevent restenosis following angioplasty in the vascular system. “Restenosis” refers to the reoccurrence of stenosis in a blood vessel or heart valve after it has been treated (as by balloon angioplasty, stenting, or valvuloplasty) with apparent success.
The treatment of a diseased site or lesion with a stent involves both delivery and deployment of the stent. “Delivery” refers to introducing and transporting the stent through a bodily lumen to a region, such as a lesion, in a vessel that requires treatment. “Deployment” corresponds to the expanding of the stent within the lumen at the treatment region. Delivery and deployment of a stent are accomplished by positioning the stent about one end of a catheter (for example the stent may be crimped onto the catheter, or onto a catheter balloon), inserting the end of the catheter through the skin into a bodily lumen, advancing the catheter in the bodily lumen to a desired treatment location, expanding the stent at the treatment location, and removing the catheter from the lumen.
Stents may also be medicated, that is manufactured to also deliver a drug, bioactive agent, or other active or bioactive agent to the patient. A medicated stent falls into the FDA definition (as per 21 CFR §3.2(e)) of a combination product due to the combination of a drug or biologic with a medical device. A medicated stent may be fabricated by coating the surface of the stent scaffolding with a polymeric carrier that includes an active or bioactive agent or drug, or in the alternative, if the stent contains a polymer, the polymer scaffolding may also serve as a carrier of an active agent or drug.
A number of techniques can be used to sterilize medical devices.
Many medical devices, such as but not limited to, stents, typically undergo terminal sterilization, that is sterilization occurs in the final packaged product, or for a stent, sterilization after fabrication, mounting on the delivery device, attachment to a delivery system and packaging. Thus, the sterilization operation may have a negative impact on the material comprising the stent or the material comprising the stent coating, and/or any drug, bioactive agents, or other additive in the coating on the stent.